6XMJ

Human 20S proteasome bound to an engineered 11S (PA26) activator

6XMJ の概要

• エントリーDOI: 10.2210/pdb6xmj/pdb
• EMDBエントリー: 22259
• 分子名称: Proteasome subunit alpha type-6, Proteasome subunit beta type-3, Proteasome subunit beta type-2, ... (15 entities in total)
• 機能のキーワード: 11s-bound, 20s proteasome, hydrolase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 21
• 化学式量合計: 523664.12

構造登録者

de la Pena, A.H.,Opoku-Nsiah, K.A.,Williams, S.K.,Chopra, N.,Sali, A.,Gestwicki, J.E.,Lander, G.C. (登録日: 2020-06-30, 公開日: 2020-07-22, 最終更新日: 2024-05-15)

主引用文献

Opoku-Nsiah, K.A.,de la Pena, A.H.,Williams, S.K.,Chopra, N.,Sali, A.,Lander, G.C.,Gestwicki, J.E.
The Y Phi motif defines the structure-activity relationships of human 20S proteasome activators.
Nat Commun, 13:1226-1226, 2022

PubMed Abstract: The 20S proteasome (20S) facilitates turnover of most eukaryotic proteins. Substrate entry into the 20S first requires opening of gating loops through binding of HbYX motifs that are present at the C-termini of certain proteasome activators (PAs). The HbYX motif has been predominantly characterized in the archaeal 20S, whereas little is known about the sequence preferences of the human 20S (h20S). Here, we synthesize and screen ~120 HbYX-like peptides, revealing unexpected differences from the archaeal system and defining the h20S recognition sequence as the Y-F/Y (YФ) motif. To gain further insight, we create a functional chimera of the optimized sequence, NLSYYT, fused to the model activator, PA26. A cryo-EM structure of PA26-h20S is used to identify key interactions, including non-canonical contacts and gate-opening mechanisms. Finally, we demonstrate that the YФ sequence preferences are tuned by valency, allowing multivalent PAs to sample greater sequence space. These results expand the model for termini-mediated gating and provide a template for the design of h20S activators.

PubMed: 35264557
DOI: 10.1038/s41467-022-28864-x

実験手法

ELECTRON MICROSCOPY (3 Å)